PROJECT SUMMARY Many lifestyle factors have been examined as possible prostate cancer risk factors, but results are inconsistent across studies. It is possible that failure to adequately account for differences in PSA screening and diagnostic intensity explains some of these inconsistencies. The introduction of PSA screening for prostate cancer in the late 1980s has had a major impact on prostate cancer epidemiology, with a sustained increase in incidence rates, a shift to more localized disease, and decreased mortality rates. Both screening and willingness to undergo a prostate biopsy, the diagnostic procedure that follows an elevated PSA, are associated with various demographic and lifestyle factors. These differences in men?s PSA screening and biopsy behaviors may distort the estimated effects of lifestyle factors on prostate cancer risk, but few attempts have been made to quantitatively assess this source of possible bias. Our scientific premise is that appropriately accounting for the impact of screening and biopsy is necessary to elucidate the underlying associations between lifestyle factors and prostate cancer risk. The objective of this project is to study the impact of screening and propensity for biopsy on the association between demographic and lifestyle factors and prostate cancer. This will support more rigorous interpretation of existing studies of prostate cancer epidemiology and inform data collection and analytic methods for future studies. We will use data from a large, on-going cohort, the Health Professionals Follow-up Study (HPFS), a unique resource which has collected information on the use of PSA screening and prostate biopsy every two years since 1996, and also has updated information on an array of lifestyle factors, and information on prostate cancer diagnosis and survival. In Aim 1, we will investigate how patterns of prostate cancer screening and biopsy are associated (a) with demographic and lifestyle factors, including: age, race, family history, smoking, obesity, physical activity, diet, and medication usage, and (b) with risk of prostate cancer. In Aim 2, we will use several analytic approaches to study how these lifestyle factors are associated with prostate cancer risk, independent of screening and biopsy practices. This study efficiently leverages a unique collection of existing data to provide the first comprehensive assessment of the impact of prostate cancer screening and diagnosis behaviors on prostate cancer risk factors. By characterizing and quantifying this detection bias, this project will aid in the interpretation of existing studies of prostate cancer risk factors and provide direction to future studies on data collection and analytic methods to better handle these issues. Overall, we hope that this work will shed light on previous inconsistencies in findings on prostate cancer risk factors and support more rigorous identification of risk factors for prostate cancer, supporting public health prevention efforts.